Adrenal Insufficiency: University company wins healthy £300k for new Cardiff-based drug

A UNIVERSITY spin-out venture yesterday won a £300,000 investment to support the commercialisation of its product.

 

Fusion IP, the university commercialisation company which turns university research into business, is investing the money into Diurnal, an innovative, early stage Fusion portfolio company from the University of Sheffield.

 

Cardiff-based Diurnal is developing a novel approach to drug delivery which will help patients suffering from reduced cortisol and testosterone levels.

 

The investment is part of a £600,000 funding round in which Finance Wales has also invested £300,000 under its memorandum of understanding with Fusion. Diurnal will have a post-money valuation of £2m.

 

Diurnal has developed a delayed and sustained release therapy to deliver hydrocortisone in a manner that mimics the body’s normal circadian rhythm – the body’s natural 24 hour hormone cycle.

 

This therapeutic approach has the potential to help patients with deficiencies in steroid hormones, testosterone, thyroid hormones and associated conditions by regulating metabolism, growth development and puberty, tissue function and in determining mood.

Each of these deficiencies requires life-long treatment and Diurnal’s approach to drug delivery has the potential to drastically improve patients’ lives, according to the company.

 

Working closely with Penn Pharma, the Tredegar-based pharmaceutical services company, and Simbec Research in Merthyr Tydfil, Diurnal will use the funding to continue to develop its new formulation approach to endocrine therapy and to complete phase one clinical trials of its lead product Chronocort, for adrenal insufficiency in the first half of next year.

 

The product has already received two related Orphan Drug designations from the European Medicines Agency, which affords 10 years of market exclusivity after the grant of marketing authorisation in Europe.

 

Martin Whitaker, general manager at Diurnal, said: “Diurnal’s product pipeline has the potential to help many patients with hormone deficiencies that disrupt the body’s natural clock.

 

“Our lead compound Chronocort is focused on delivering a delayed and sustained release therapy. Following positive pre-clinical results and today’s fundraising, Chronocort is poised to enter phase one clinical trials next year.

 

“In addition, it has significant market potential and has already received Orphan Drug Designation potentially giving it market exclusivity in Europe.”

 

Following the fundraising Fusion will have a 51.6% shareholding in Diurnal.

David Baynes, chief executive officer of Fusion IP, said: “Diurnal’s endocrine therapies have great potential for patients suffering from hormone deficiencies.

 

“Taking Chronocort into phase I clinical trials next year is a major step forward for Diurnal and we are delighted to see the company making such positive progress.”

 

Jocelyn Brown, Associate at Finance Wales, said: “This latest funding round accelerates Diurnal’s commitment to creating niche therapeutics targeting areas of greatest unmet patient need.

 

“The continuing success of Diurnal is underpinned by their strong partners within the Welsh biosciences community, and we’re pleased to be investing in such a dynamic, forward-looking company.”

 

 

From http://www.walesonline.co.uk/business-in-wales/business-news/2009/12/08/university-company-wins-healthy-300k-for-new-cardiff-based-drug-91466-25341981/

Online Survey for Adrenal Insufficiency

Eric Fiedler, founder and co-leader of the Baltimore/D.C. Addison's Support Group, is conducting a survey of adrenal insufficient (Addison's disease and secondary adrenal insufficiency) patients.

Eric is a senior at Johns Hopkins University in Baltimore, Maryland, working toward degrees in neuroscience. This survey is being used as Eric's Undergraduate Research Project. He has the backing of Johns Hopkins University and is conducting the survey under the supervision of Dr. Roberto Salvatori.

Dr. Salvatori is an endocrinologist at Johns Hopkins University who specializes in adrenal and pituitary diseases. He also is one of the foremost researchers in adrenal disease as well as control of growth hormone secretion, genetic causes of growth hormone deficiency, consequences of growth hormone deficiency.

Access Eric's survey here "Qualitative Study on Cushingoid Syndrome Associated with Corticosteroid Replacement Therapy" or on the NADF Website (www.nadf.us).

The survey should be completed by patients who have adrenal insufficiency, with the exclusion of those who have adrenal insufficiency due to adrenoleukodystrophy, adrenomyeloneuropathy, congenital adrenal hyperplasia (all types) and/or AIDS.

Thank you so much for your participation!

Diagnosis of Adrenal Insufficiency Using the GHRP-6 Test: Comparison with the Insulin Tolerance Test in Patients with Hypothalamic-Pituitary-Adrenal Disease

B. Alaioubi¹, K. Mann¹, S. Petersenn¹

¹ Department of Endocrinology and Division of Laboratory Research, University of Duisburg-Essen, Essen, Germany

Abstract

The insulin tolerance test (ITT) is considered the gold standard for the diagnosis of adrenal insufficiency (AI). However, the test is unpleasant to perform and has the risk of serious complications. We therefore evaluated the clinical applicability of GHRP6, which is a known activator of the hypothalamic-pituitary-adrenal (HPA) axis, to test for AI. For this purpose a comparative clinical study was designed.

 

Forty-nine patients with suspected dysfunction of the HPA axis and 20 healthy controls were enrolled. The ITT was performed in patients, and GHRP6 (1 μg/kg) testing in patients and controls. Serum cortisol over 90 min after GHRP6, in comparison to the ITT, was the main outcome measure.

 

Thirty-one patients had a peak cortisol response of less than 500 nmol/l during ITT and were considered adrenal insufficient. For GHRP6, the mean cortisol peak was 227±25.7 nmol/l in the AI group versus 395±35.3 nmol/l in the adrenal sufficient (AS) group. ROC analysis of peak cortisol levels during GHRP6 test suggested an optimal threshold of 299 nmol/l for the diagnosis of AI (Sens. 71.0%, Spec. 77.8%). Applying upper (416 nmol/l) and lower (137 nmol/l) thresholds with high specificities in combination with early morning cortisol established the diagnosis in nearly half of the patients, even when the GHRP6 test is limited to 30 min duration. GHRP6 led to significant activation of the HPA axis with no detectable side effects, but had limited accuracy in comparison to the ITT.

Key words

growth hormone secretagogues - ghrelin - insulin tolerance test

 

From http://www.thieme-connect.de/ejournals/abstract/hmr/doi/10.1055/s-0029-1243184

Jane Austen 'died of tuberculosis not hormonal disorder'

Jane Austen probably died of tuberculosis after drinking unpasteurised milk rather than falling victim to a rare hormonal disorder as is generally assumed, research shows.

 

By Matthew Moore
Published: 8:00AM GMT 01 Dec 2009

 

 

The Pride and Prejudice novelist's premature death aged just 41 has long fascinated medical historians, with several explanations offered for her assorted and curiously mild symptoms.

 

Most biographers have accepted a posthumous diagnosis published in 1964 that she was one of the first known sufferers of Addison's disease, in which patients' adrenal glands fail to produce sufficient steroid hormones.

 

But a new reading of Austen's letters indicates that the Emma and Persuasion author was far too lucid in her final days in 1817 to have been dying of Addison's, whose victims usually endure a loss of concentration bordering on delirium as their condition worsens.

 

Austen was part way through her seventh novel Sandition when she succumbed to the sickness that had dominated her past two years, and was cogent enough to dictate lines of comic verse from her sick bed just 48 hours before her death.

 

Two months earlier she had written to a friend: "My head was always clear, and I had scarcely any pain."

 

Katherine White, a scholar and Addison's sufferer, wrote in the Medical Humanities journal that this evidence alone appears to rule out Addison's.

 

"While Austen was undoubtedly an exceptional intellect, this clarity of thought is not typical of advanced adrenal failure," she wrote.

 

"Extreme sleepiness, slurred speech, confusion or a semi-conscious state of characteristic of adrenal crises."

 

Addison's was first proposed as the cause of Austen's death by Sir Zachary Cope, a respected surgeon who specialised in abdominal conditions.

 

He based his diagnosis – proposed nearly 150 years after her death – on letters sent by the author in which she lamented her bed-ridden exhaustion, bilious attacks and rheumatic pains. Austen's skin also changed tone, turning "black and white and every wrong colour" as she wrote in a letter to her niece.

 

While acknowledging that these symptoms could indicate Addison's, Mrs White argues that an apparent improvement in Austen's condition as death approached pointed to alternative explanations.

 

"The absence of pain during her final months is revealing: intense migraine-like headache and generalised arthralgias are the norm for contemporary patients." she wrote.

 

That the comic writer did not appear to suffer severe weight loss further undermines the Addison's diagnosis, according to White.

 

She suggests that disseminated tuberculosis affecting the joints and liver – which Sir Zachary proposed as a possible cause of the Addison's – offers a "simpler" and sufficient explanation for Austen's symptoms, particularly as it was rife in the early 19th Century.

 

The infection likely had bovine origins, she adds, suggesting Austen may have ingested bacteria by drinking milk that had not been treated, like many of her contemporaries.

Austen died in the Hampshire town of Winchester where she had travelled for medical treatment. She was buried in Winchester Cathedral.

 

Historians have struggled to decipher the private life of the woman behind some of the most enigmatic characters in English literature because her sister Cassandra burned many of her letters and documents after her death.

 

Tuberculosis was the biggest killer in 19th century Britain, but today almost all strains can be controlled by antibiotics. Addison's disease used to be fatal but steroid replacement therapy now allows most sufferers to live a normal life.

 

From http://www.telegraph.co.uk/culture/books/booknews/6692503/Jane-Austen-died-of-tuberculosis-not-hormonal-disorder.html

Isolated Addison’s is unlikely to be caused by mutations in MC2R, MRAP or StAR, three genes responsible for familial glucocorticoid deficiency

Renuka Dias, Li Chan, Louise Metherell, Simon Pearce and Adrian Clark

R Dias, Centre for Endocrinology, Queen Mary University of London, London, ec1m 6bq, United Kingdom
L Chan, Centre for Endocrinology, QMUL, London, United Kingdom
L Metherell, Centre for Endocrinology, QMUL, London, United Kingdom
S Pearce, Institute of Human Genetics, Centre for Life, Newcastle-upon-Tyne, United Kingdom

A Clark, Centre for Endocrinology, QMUL, London, United Kingdom

Correspondence: Renuka Dias, Email: r.dias@qmul.ac.uk

 

Background

Familial Glucocorticoid Deficiency (FGD) is a rare autosomal recessive disease caused by ACTH resistance and leads to isolated glucocorticoid deficiency. Although FGD patients typically have normal mineralocorticoid secretion, subtle alterations in the renin-angiotensin-aldosterone axis have been reported in a subset of patients at presentation. Anecdotally some patients with FGD have been initially diagnosed as having AD, with implications for treatment and genetic counselling. Currently mutations in 3 genes: the ACTH receptor (MC2R); the melanocortin 2 receptor accessory protein (MRAP) and the Steroidogenic Acute Regulatory protein (StAR) are known to give rise to FGD types 1-3. We investigated a cohort of autoantibody-negative AD patients for mutations in these genes .

 

Methods

40 patients with known AD without evidence of autoimmune disease were screened for mutations in MC2R, MRAP and StAR . In addition patients were genotyped for the MC2R promoter polymorphism previously associated with reduced responsiveness to ACTH.

 

Results

No mutations in MC2R, MRAP or StAR were identified in any patient. The frequencies of the MC2R promoter polymorphism were similar to those reported in healthy controls.

 

Conclusions

FGD does not appear be underdiagnosed in the AD population. However, in ~50% of patients with FGD no genetic cause has yet been identified and it is possible that the other, as yet unidentified genes giving rise to FGD maybe implicated in AD.

 

From http://www.eje.org/cgi/content/abstract/EJE-09-0720v1

Are doctors ever really off duty?

I found this article especially interesting.  This question was asked of a group of endos at an NIH conference a few years ago - if you saw someone on the street who looked like they had symptoms of fill-in-the disease, would you suggest that they see a doctor.  The general answer was no.  No surprise there. 

Patients, if you see someone who looks like s/he has Cushing's, give them a discrete card.

Spread The Word! Cushing's Pocket Reference

Robin Writes:

This has been a concern of mine for some time. Your post spurred me on to do something I've been meaning to do. I've designed something you can print that will fit on the business cards you can buy just about anywhere (Wal-mart included). You can also print on stiff paper and cut with a paper cutter or scissors. I've done a front and a back.

Here are the links:

• Front: This card is being presented by a person who cares.
• Back (The same for everyone)

This Topic on the Message Boards

~~~~~~~~~~~~~~~~~~

And now, the article from http://www.guardian.co.uk/lifeandstyle/2009/nov/03/doctor-diagnosis-stranger:

Are doctors ever really off duty?

Which potentially serious symptoms would prompt them to stop and advise a stranger on a bus?

By Lucy Atkins

• 
  • Lucy Atkins
  • The Guardian, Tuesday 3 November 2009
    Article history

Passengers on a London bus. Photograph: David Levene

A Spanish woman of 55, Montse Ventura, recently met the woman she refers to as her "guardian angel" on a bus in Barcelona. The stranger – an endocrinologist – urged Ventura to have tests for acromegaly, a rare disorder involving an excesss of growth hormone, caused by a pituitary gland tumour. How had the doctor made this unsolicited diagnosis on public transport? Apparently the unusual, spade-like shape of Ventura's hands was a dead giveaway.

But how many off-duty doctors would feel compelled to alert strangers to symptoms they spot? "If I was sitting next to someone on a bus with a melanoma, I'd say something or I wouldn't sleep at night," says GP Mary McCullins. "We all have a different threshold for interfering and you don't want to terrify people, but this is the one thing I'd urge a total stranger to see a doctor about." So what other symptoms might prompt a doctor to approach someone on the street?

Moon face

Cushing's syndrome is another rare hormone disorder which can be caused by a non-cancerous tumour in the pituitary gland. "A puffy, rounded 'moon face' is one of the classic signs of Cushing's," says Dr Steve Field, chair of the Royal College of GPs. "In a social situation, I wouldn't just say, 'You're dangerously ill' but I'd try to elicit information and encourage them to see a doctor."

Different-sized pupils

When one pupil is smaller than the other, perhaps with a drooping eyelid, it could be Horner's syndrome, a condition caused when a lung tumour begins eating into the nerves in the neck. This can be the first obvious sign of the cancer. "I'd encourage someone to get this checked out," says Dr Simon Smith, consultant in emergency medicine at the Oxford Radcliffe Hospitals Trust. "People often have an inkling that something's wrong, and you might spur them to get help sooner."

Clubbing fingers

Some people are born with club-shaped fingers, but if, over time, they become "drumstick-like", this could signify serious problems such as lung tumours, chronic lung infections or congenital heart disease. "Because it happens gradually, some people disregard clubbing," says Smith. "But I'd say something because it can be an important symptom in many serious illnesses."

Lumpy eyelids

Whitish yellowy lumps around the eyelids can be a sign of high cholesterol, a major factor in heart disease. Sometimes you also get a yellow circle around the iris. "I would suggest they got a cholesterol test with these symptoms," says Smith. "They can do something about it that could save their life."

Suntan in unlikely places

A person with Addison's disease, a rare but chronic condition brought about by the failure of the adrenal glands, may develop what looks like a deep tan, even in non sun-exposed areas such as the palms. Other symptoms (tiredness, dizziness) can be non-specific so the condition is often advanced by the time it is diagnosed. Addison's is treatable with lifelong steroid replacement therapy. "If someone was saying they hadn't been in the sun but had developed a tan, alarm bells would ring and I'd probably ask how they were feeling," says McCullins.

Trench mouth

Putrid smelling breath – even if the teeth look perfect – can be a sign of acute necrotising periodontitis. "I'd be able to tell when someone walks through the door," says dentist Laurie Powell. "But people become accustomed to it and don't notice." Untreated, the condition damages the bones and connective tissue in the jaw. It can also be a sign of other diseases such as diabetes or Aids.

8 new Cushing's bios added. dx include 1 pituitary, 1 diagnosed not sure of type, 6 undiagnosed at http://ow.ly/vt0D or http://ow.ly/vt1n

Münchausen By Media - what do you think? http://ow.ly/vgEn

Cushing's locations page updated, 9 new people added from England, USA. http://ow.ly/vgop

<~~ not observant. Your blog was already there! @CatONineTales